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Serological Tests For Acquired Syphilis in Immuno Competent Patients
Serological Tests For Acquired Syphilis in Immuno Competent Patients
competent Patients
Zoran GOLUŠIN1,2, Marina JOVANOVIĆ1,2, Milan MATIĆ1,2,
Ljuba VUJANOVIĆ1,2, Tatjana ROŠ1,2, Biljana JEREMIĆ1,2
1Faculty of Medicine, University of Novi Sad, Serbia
2Clinic of Dermatovenereology Diseases, Clinical Center of Vojvodina, Novi Sad,Serbia
*Correspondence: Zoran Golušin, E-mail: zgolusin@eunet.rs
UDC 616.972-07
Abstract
Serological tests represent a valuable tool for the diagnosis and monitoring the syphilis
treatment. Non treponemal antibodies are nonspecific to detect the infection, but antibody titers
are used to monitor the effects of syphilis treatment. A definitive diagnosis of syphilis is made
using treponemal tests, because they detect specific antibodies to the treponemal strains or
treponemal fragments, which cause syphilis. These tests may remain reactive for years,
sometimes for life, regardless of the therapy outcome. Even after successful treatment,
approximately 85% of patients remain positive for treponemal antibodies for the rest of their
lives. However, treponemal tests cannot differentiate past infections from a current infection.
Therefore, we use a combination of specific and non-specific tests, the two most frequently
used diagnostic algorithms. The traditional algorithm begins with a non-treponemal assay, and
if it is positive, the treponemal test is done. A positive treponemal test indicates syphilis. The
reverse serology algorithm detects early, primary, and treated syphilis that may be missed with
traditional screening. However, non-treponemal test is necessary to detect patients with active
syphilis.
Key words
Syphilis; Syphilis Serodiagnosis; Serologic Tests; Treponema pallidum; Algorithms;
Immunocompetence; Review
In the absence of microbiological diagnosis, serological antibody tests are the mainstay
of laboratory diagnosis for all stages of syphilis other than primary. The diagnosis of syphilis
is not simple due to the fact that there is no single serological test to diagnose syphilis or
monitor the effects of treatment. Treponema pathogenic for humans has the same antigens and
a high degree of concordance of DNA, complicating the interpretation of serological tests in
geographic areas with endemic treponematoses. The clinical presentation of acquired syphilis
is so varied, that definitive diagnosis is made only by serological testing. Serological tests are
divided into two groups: non-treponemal and treponemal tests.
Non-treponemal Test
Non-specific serological tests detect IgM and IgG antibodies (anticardiolipin
antibodies) which react with cardiolipin, lecithin and cholesterol from treponema, but also with
the same lipid material from damaged host cells. Therefore, these antibodies are not specific to
confirm Treponema pallidum infection, but they indicate a tissue damage caused by the
infection. Today, the most commonly used non-treponemal tests are the following: :
VDRL (Venereal Disease Research Laboratory)
flocculation test. Inactivated serum or cerebrospinal fluid, without a
complement, given the blurring (”floc”) if it is added an antigen (cardiolipin). Examine
under a microscope..
RPR (Rapid Plasma Reagin)
a variant of VDRL test with colored substances for macroscopic reading. It is
used when quick view of a large number of sera is necessary. Both of these tests use
cardiolipin, a phospholipid, combined with lecithin and cholesterol, as the active
antigen for the detection of antibodies suggestive of syphilis (1).
These tests are done manually. They are not automated, so the interpretation of
results is subjective. Non-specific antibodies appear about 6 weeks after the infection
(2, 3). During the primary stage, these antibodies have low titers (≤1: 4) and they are
present in 40% of infected subjects, while in the secondary stage low antibody titers are
present in only in 11% of patients (4). The highest antibody titer is seen in the secondary
stages of syphilis, from 1:16 to 1: 256, and declines thereafter, typically falling to 1:4
or ot lower in untreated late-latent infection. The advantage of these tests is that they
are quick and cheap. The antibody titers mostly correlate with the disease activity. The
results should be reported quantitatively, and as such they are used to monitor disease
activity and efficacy of treatment. Therefore it is necessary to determine the antibody
titer (quantitative VDRL/ RPR) on the day of treatment initiation. After healing, the
antibody titers are reduced or completely absent. Quantitative non-treponemal testing
can also be used to determine if a patient, who appears to have failed treatment, has
been re-infected or is “serofast”. Serofast patients fail to fully resolve serologically and
perpetually exhibit low non-treponemal titers, whereas re-infected patients have
persistently higher antibody titers (5). The VDRL and RPR are equally valid assays,
but quantitative results from the two tests cannot be compared directly because RPR
titers are commonly slightly higher than VDRL titers.
The limitation of these tests is frequent occurrence of false positive or false
negative reactions. False positive reactions may be acute (lasting for 6 months) and
chronic (lasting longer than 6 months) and account for 20% of tests. Acute false positive
reactions may be seen in the post-immunization period, after recent myocardial
infarction and in many febrile infectious diseases (e.g. malaria, hepatitis, chicken pox,
measles, etc.), and possibly during pregnancy. Chronic false positive reactions may be
seen in injecting drug users, autoimmune diseases, HIV infection, chronic infections
such as leprosy, malignancies, chronic liver disease and older age. Also, false positive
reactions are due to connective tissue disorders, and Lyme disease. False negative
results are obtained in too early or too late stage of infection, when the antibody titers
are low, or in the secondary stage of syphilis, with high antibody titers and there is no
agglutination – the so-called prozone phenomenon, which occurs in 1 - 2% of patients,
usually in pregnant women and HIV infected patients (2, 6, 7, 8).
Generally, up to 90% of false-positive reactions have a titer of less than 1:8, and
reactive non-treponemal tests with titers less than 1:8 and subsequent nonreactive
treponemal tests are considered to be biological false-positive reactions (2).
Treponemal Test
The treponemal tests are used for definitive diagnosis of syphilis because they detect
specific antibodies (antiterponemal antibodies) utilizing either whole cells or antigens derived
from cells of T. Pallidum causinge syphilis. Specific tests become reactive before nonspecific,
but unlike them, they remain reactive for years, sometimes for life, regardless of therapy
outcome. Even after successful therapy, approximately 85% of patients remain positive for
treponemal antibodies for life (9). However, 15 - 25% of patients treated during the primary
stage revert to being serologically nonreactive after 2 - 3 years (10). Therefore, treponemal
tests are not used to monitor disease activity, as well as to distinguish active from treated
syphilis. The most commonly used specific tests are :